Background: Diffuse large B cell lymphoma (DLBCL) and related entities are the commonest type of non-Hodgkin lymphomas. There are several distinct immunohistochemical subgroups of the DLBCL within the “not otherwise specified” (NOS) category. We evaluated a series of 449 aggressive B cell lymphomas and identified 17 cases of DLBCL with CD5 expression, excluding cases of transformation of chronic lymphocytic leukemia or mantle cell lymphoma. These were further evaluated comparing their immunohistochemical and genetic profiles.Design: 449 cases were evaluated using an extensive panel of immunohistochemical stains (CD20, CD3, CD5, CD10, cyclin D1, bcl6, bcl2, EBER, Ki67, and CD30) and a panel of FISH studies (including MYC, IGH/BCL2 and BCL6). In this series we identified 17 cases (3.8%) of DLBCL with CD5 expression by immunohistochemistry. Seven (41%) of these were nodal and ten (59%) were extranodal.Results: All 17 de novo CD5 positive DLBCL were immunohistochemically positive for BCL2 expression (100%). Only 31% (5/16) were positive for CD10, whereas 75% (12/16) showed BCL6 expression and 81% (13/16) showed MUM1 positivity. In this regard, the majority of cases showed a non-germinal-center-cell phenotype by both the Hans classifier (9/15; 60%), as well as the Tally classifier (7/8; 88%). Of note, none showed CD30 expression (0/5) and none showed evidence of EBV by ISH studies (0/14). FISH studies were performed on 13/17 cases. Notably, no case was positive for the MYC gene rearrangement (0/17). IgH/BCL2 fusion was seen in 2/13 (15%) cases, and the BCL6 translocation was seen in 4/13 (31%) cases. Both the IGH/BCL2 positive cases also had BCL6 rearrangement.Conclusions: Our series reveals that de novo CD5+ DLBCLs are a small but significant subgroup of the aggressive B-cell lymphomas. They show variation in clinicopathologic features, immunophenotype and genetics. Many are extranodal and are mainly classified as the no-germinal center B-cell type, suggesting a mechanism to their clinical aggressiveness. They lack MYC translocations and are not usually associated with EBV infection. Further a small but significant subset harbor both IGH/BCL2 and concurrent BCL6 translocations. These features are in contrast to other types of nodal and extranodal aggressive B cell lymphomas.Category: Hematopathology